Examining the role of endogenous cardiotonic steroids in cardiovascular disease development

Cardiovascular disease is one of the leading causes of death in the UK and USA. Experimental evidence from animals suggests that chronic elevation of cardiotonic steroids (CTS) may play a pivotal role in development of cardiovascular disease. However, the chemical identity of CTS and their pathophysiological role in patients with cardiovascular disease remains unclear.

We will develop novel, sensitive, analytical liquid chromatography–mass spectrometry (LC-MS) techniques for detection and quantification of CTS in the serum. We will measure CTS serum concentrations in individual patients and the effects of serum on intracellular sodium and calcium concentrations in human-induced pluripotent stem-cell-derived cardiomyocytes. We will correlate the analytical and functional data we obtain with clinical cardiovascular parameters and functional outcomes in individual patients.

By generating fundamental tools that quantify individual CTS species in the serum and characterising their effects on sodium and calcium regulation in human cardiomyocytes, this study aims to provide crucial clinical information on the role of CTS in development of cardiovascular disease which will help with the development of management strategies for the disease.